Protein glycosylation as Critical Quality Attribute (CQA) on therapeutic antibodies
Protein glycosylation is considered to be one of the critical quality attributes (CQAs) known to affect the safety and efficacy of a given drug. In the case of therapeutic monoclonal antibodies, glycosylation is commonly recognized to be a factor in terms of product stability, structural conformation, and functional activity.
GlycoMScan offers complete glycan occupancy analysis with an accuracy of down to 0.1% using a unique combination of high resolution chromatography and sensitive fluorescence detection detection together with targeted mass spectrometry for even the lowest abundant glycans, such as the high mannose glycans on therapeutic antibodies.
We have access to glycan databases containing more than 25,000 glycan structures for accurate identification. The method yields N-Glycans in stoichiometric amounts with no detectable loss of sialic acid and allows for picomolar quantitation.
We recommend this analysis for production of biosimilars and in-depth characterization of mono- and polyclonal antibody batches.
Our expertise is the analysis of protein glycosylation. Protein glycosylation is considered to be one of the critical quality attributes (CQAs) known to affect the safety and efficacy of a given drug. In the case of therapeutic monoclonal antibodies, glycosylation is commonly recognized to be a factor in terms of product stability, structural conformation, and functional activity.
We analyze intact proteins, free N-glycans or in-between sizes, like middle-down analyses, dependent on the research question. Glycomics of biofluids such as plasma, saliva or csf is another possibility to profile the whole complex mixture of glycoproteins.
Detailed structural information can be obtained from a glycan of interest by MS-MS fragmentation analyses.
Due to our unique background, we are able to analyze nucleotide sugars, the building blocks of glycosylation, with a superior resolution and sensitivity in cells, bacteria or tissues. Furthermore, we can do this within a timeseries, thereby visualizing the flow of these compounds through the metabolic processes within the cell. This enables us to identify bottlenecks in the availability of substrates for the production of for example monoclonal antibodies.
That this field of glycosylation analysis is still somewhat of a niche, is also written in a recent article in Pharmaceutical Technology: S. Haigney, “Outsourcing Glycan Analysis,” Pharmaceutical Technology 42 (8) 2018.
There isn’t a single methodology that covers all glycan analysis needs. For example if you need to select clones for your quality target product profile or for batch release, our toolbox will be adapted to your specific needs.